Eukaryotic hexosamine biosynthesis and GlcNAc salvage

A reusable eukaryotic pathway that converts fructose 6-phosphate to UDP-N-acetylglucosamine through glutamine-dependent amination, acetyl-CoA- dependent N-acetylation, phosphomutase conversion, and UTP-dependent uridylyl transfer. A GlcNAc-kinase salvage branch enters at the N-acetylglucosamine 6-phosphate intermediate. Feedback inhibition of GFAT by UDP-GlcNAc couples pathway flux to nutrient availability and glycosylation demand. The product supplies protein and lipid glycosylation, proteoglycan and GPI-anchor synthesis, O-GlcNAcylation, and the GNE-dependent sialic-acid route.

MODULE:hexosamine_biosynthesisDRAFTCONCRETEMetabolic Pathwaymodules/hexosamine_biosynthesis.yaml

UDP-N-acetylglucosamine biosynthetic processGO:0006048 UDP-N-acetylglucosamine metabolic processGO:0006047

GO:0006048

UDP-N-acetylglucosamine biosynthetic process

GFPT1/2, GNPNAT1, PGM3 and UAP1 carry out UDP-GlcNAc biosynthesis (GO:0006048).

GO:0006047

UDP-N-acetylglucosamine metabolic process

NAGK salvages free GlcNAc into the UDP-GlcNAc metabolic pathway (GO:0006047).

file:human/GFPT1/GFPT1-ai-review.yaml

GFPT1 gene review (human)

The rate-limiting Fru-6-P + Gln -> GlcN-6-P step (UniProtKB:Q06210, GO:0004360) matches the completed human GFPT1 review.

file:human/GFPT2/GFPT2-ai-review.yaml

GFPT2 gene review (human)

The Fru-6-P + Gln -> GlcN-6-P step (UniProtKB:O94808, GO:0004360) matches the completed human GFPT2 review.

file:human/GNPNAT1/GNPNAT1-ai-review.yaml

GNPNAT1 gene review (human)

The GlcN-6-P -> GlcNAc-6-P acetylation step (UniProtKB:Q96EK6, GO:0004343) matches the completed human GNPNAT1 review.

file:human/PGM3/PGM3-ai-review.yaml

PGM3 gene review (human)

The GlcNAc-6-P <-> GlcNAc-1-P mutase step (UniProtKB:O95394, GO:0004610) matches the completed human PGM3 review.

file:human/UAP1/UAP1-ai-review.yaml

UAP1 gene review (human)

The GlcNAc-1-P + UTP -> UDP-GlcNAc step (UniProtKB:Q16222, GO:0003977) matches the completed human UAP1 review.

file:human/NAGK/NAGK-ai-review.yaml

NAGK gene review (human)

The GlcNAc salvage kinase step (UniProtKB:Q9UJ70, GO:0045127) matches the completed human NAGK review.

6Nodes

5Parts

0Variant Sets

0Variants

5Annotons

4Connections

Derived QC

Recommended-field compliance

60.0% recommended fields populated

module.knowledge_gaps[0] · status (0/1)
module.knowledge_gaps[0] · provenance (0/1)

Module deep research

✗ none found

No MODULE:hexosamine_biosynthesis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (6/6 grounded genes reviewed)

6 complete review(s) · 0 with deep research · 0 missing review · 6 reviewed but lacking deep research

Gene	Review	Complete	Deep research
GFPT1 Q06210	✓	✓	✗
GFPT2 O94808	✓	✓	✗
GNPNAT1 Q96EK6	✓	✓	✗
NAGK Q9UJ70	✓	✓	✗
PGM3 O95394	✓	✓	✗
UAP1 Q16222	✓	✓	✗

Tree

Eukaryotic hexosamine biosynthesis and GlcNAc salvageMetabolic Pathwayhexosamine_biosynthesis

Parts
1. 1. amidotransfer (rate-limiting; Fru-6-P + Gln)
2. Glutamine:fructose-6-phosphate amidotransferase (GFPT1/GFPT2)Reactiongfpt_amidotransfer
  
  Annotons
  - GFPT1/GFPT2: glutamine-fructose-6-phosphate transaminase (isomerizing) Family: GFPT / GFAT amidotransferase family
3. 2. N-acetylation (acetyl-CoA)
4. Glucosamine-6-phosphate N-acetyltransferase (GNPNAT1)Reactionglcn6p_acetylation
  
  Annotons
  - GNPNAT1: glucosamine-6-phosphate N-acetyltransferase Family: GNPNAT1 / GNA1 (GNAT) acetyltransferase family
5. 3. phosphohexomutase (6-P <-> 1-P)
6. Phosphoacetylglucosamine mutase (PGM3)Reactionglcnac_mutase
  
  Annotons
  - PGM3: phosphoacetylglucosamine mutase Family: PGM3 / alpha-D-phosphohexomutase family
7. 4. uridylyltransfer (UTP -> UDP-GlcNAc)
8. UDP-N-acetylglucosamine pyrophosphorylase (UAP1)Reactionudp_glcnac_synthesis
  
  Annotons
  - UAP1: UDP-N-acetylhexosamine pyrophosphorylase Family: UAP1 / UDP-N-acetylhexosamine pyrophosphorylase family
9. 5. GlcNAc salvage (recycling)
10. N-acetylglucosamine kinase (NAGK)Reactionglcnac_salvage
  
  Annotons
  - NAGK: N-acetylglucosamine kinase Family: NAGK / N-acetylglucosamine kinase family

Details

Context

eukaryotesNCBITaxon:2759

cytosolGO:0005829

Eukaryotic hexosamine biosynthesis and GlcNAc salvageMetabolic Pathwayhexosamine_biosynthesis

UDP-N-acetylglucosamine biosynthetic processGO:0006048 UDP-N-acetylglucosamine metabolic processGO:0006047

Context

eukaryotesNCBITaxon:2759

cytosolGO:0005829

Eukaryotic hexosamine biosynthesis / UDP-GlcNAc synthesis (GO:0006048 + GO:0006047), grounded to six completed human gene reviews. Linear route: GFPT1 (Q06210, rate-limiting, feedback- inhibited) + tissue-restricted paralog GFPT2 (O94808) share PTHR10937, GO:0004360 (Fru-6-P + Gln -> GlcN-6-P) -> GNPNAT1 (Q96EK6 PTHR13355, GO:0004343 acetyl-CoA acetylation -> GlcNAc-6-P) -> PGM3 (O95394 PTHR45955, GO:0004610 Mg-mutase -> GlcNAc-1-P) -> UAP1 (Q16222 PTHR11952, GO:0003977 + UTP -> UDP-GlcNAc). SALVAGE: NAGK (Q9UJ70 PTHR12862, GO:0045127 + ATP) recycles free GlcNAc to GlcNAc-6-P, re-entering at the PGM3 node. UDP-GlcNAc is the universal amino-sugar donor feeding the sialic-acid (GNE), glycosphingolipid, N-/O-glycosylation and O-GlcNAc modules curated elsewhere — this module is their upstream source. GFPT1 is UDP-GlcNAc-feedback-inhibited, making the pathway a nutrient/flux sensor. Notable moonlighting captured in the gene reviews (kept non-core here): UAP1 protein-serine pyrophosphorylase (IRF3, type-I-IFN) and NAGK muramyl-dipeptide kinase (NOD2). GO term ids/labels verified against the local go.db. Disorders: GFPT1 CMS12, GNPNAT1 rhizomelic skeletal dysplasia, PGM3-CDG.

Connections

gfpt_amidotransfer -> glcn6p_acetylation Provides Input For

The GlcN-6-P made by GFPT1/2 is N-acetylated by GNPNAT1.

glcn6p_acetylation -> glcnac_mutase Provides Input For

The GlcNAc-6-P made by GNPNAT1 is converted to GlcNAc-1-P by PGM3.

glcnac_mutase -> udp_glcnac_synthesis Provides Input For

The GlcNAc-1-P made by PGM3 is the substrate for UAP1.

glcnac_salvage -> glcnac_mutase Provides Input For

NAGK feeds salvaged GlcNAc-6-P into the pathway at the PGM3 step (the same node GNPNAT1 produces), recycling free GlcNAc from glycoconjugate degradation into UDP-GlcNAc.

Part 1: amidotransfer (rate-limiting; Fru-6-P + Gln)

Glutamine:fructose-6-phosphate amidotransferase (GFPT1/GFPT2)Reactiongfpt_amidotransfer

Annotons

GFPT1/GFPT2: glutamine-fructose-6-phosphate transaminase (isomerizing)

gfpt_activity

Participant: Family: GFPT / GFAT amidotransferase family

Family:

GFPT / GFAT amidotransferase familyPANTHER:PTHR10937

Representative Members: GFPT1 (human; ubiquitous, rate-limiting)UniProtKB:Q06210 GFPT2 (human; tissue-restricted)UniProtKB:O94808

Function

L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activityGO:0004360

Substrates: D-fructose 6-phosphate L-glutamine

Products: D-glucosamine 6-phosphate L-glutamate

Aminate Fru-6-P with glutamine to GlcN-6-P (rate-limiting HBP step).

Part 2: N-acetylation (acetyl-CoA)

Glucosamine-6-phosphate N-acetyltransferase (GNPNAT1)Reactionglcn6p_acetylation

Annotons

GNPNAT1: glucosamine-6-phosphate N-acetyltransferase

gnpnat1_activity

Participant: Family: GNPNAT1 / GNA1 (GNAT) acetyltransferase family

Family:

GNPNAT1 / GNA1 (GNAT) acetyltransferase familyPANTHER:PTHR13355

Representative Members: GNPNAT1 (human)UniProtKB:Q96EK6

Function

glucosamine 6-phosphate N-acetyltransferase activityGO:0004343

Substrates: D-glucosamine 6-phosphate acetyl-CoA

Products: N-acetyl-D-glucosamine 6-phosphate coenzyme A

N-acetylate GlcN-6-P to GlcNAc-6-P (acetyl-CoA).

Part 3: phosphohexomutase (6-P <-> 1-P)

Phosphoacetylglucosamine mutase (PGM3)Reactionglcnac_mutase

Annotons

PGM3: phosphoacetylglucosamine mutase

pgm3_activity

Participant: Family: PGM3 / alpha-D-phosphohexomutase family

Family:

PGM3 / alpha-D-phosphohexomutase familyPANTHER:PTHR45955

Representative Members: PGM3 (human)UniProtKB:O95394

Function

phosphoacetylglucosamine mutase activityGO:0004610

Substrates: N-acetyl-D-glucosamine 6-phosphate

Products: N-acetyl-D-glucosamine 1-phosphate

Interconvert GlcNAc-6-P and GlcNAc-1-P (Mg2+).

Part 4: uridylyltransfer (UTP -> UDP-GlcNAc)

UDP-N-acetylglucosamine pyrophosphorylase (UAP1)Reactionudp_glcnac_synthesis

Annotons

UAP1: UDP-N-acetylhexosamine pyrophosphorylase

uap1_activity

Participant: Family: UAP1 / UDP-N-acetylhexosamine pyrophosphorylase family

Family:

UAP1 / UDP-N-acetylhexosamine pyrophosphorylase familyPANTHER:PTHR11952

Representative Members: UAP1 (human)UniProtKB:Q16222

Function

UDP-N-acetylglucosamine diphosphorylase activityGO:0003977

Substrates: N-acetyl-D-glucosamine 1-phosphate UTP

Products: UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) diphosphate

Condense GlcNAc-1-P + UTP to UDP-GlcNAc (final step).

Part 5: GlcNAc salvage (recycling)

N-acetylglucosamine kinase (NAGK)Reactionglcnac_salvage

Annotons

NAGK: N-acetylglucosamine kinase

nagk_activity

Participant: Family: NAGK / N-acetylglucosamine kinase family

Family:

NAGK / N-acetylglucosamine kinase familyPANTHER:PTHR12862

Representative Members: NAGK (human)UniProtKB:Q9UJ70

Function

N-acetylglucosamine kinase activityGO:0045127

Substrates: N-acetyl-D-glucosamine (free; from glycoconjugate turnover) ATP

Products: N-acetyl-D-glucosamine 6-phosphate ADP

Phosphorylate free GlcNAc to GlcNAc-6-P (salvage into the HBP).